The Drug Enforcement Administration issued a final order Friday placing an extremely potent street drug on the schedule of controlled substances after dozens of deaths.

Acetyl fentanyl, which the agency says is 15.7 times more potent than morphine and up to five times more powerful than heroin, is particularly dangerous because the range between the effective dose and the lethal dose is narrow.

The Center of Disease Control issued an alert on acetyl fentanyl in June 2013, after 14 deaths in Rhode Island were attributed to the drug over a three month period.

A total of 39 known deaths have been reported in Rhode Island, North Carolina, California, Louisiana, Oregon and Pennsylvania.

But the Drug Enforcement Administration says it is likely that emergency room admissions and deaths due to this drug are under-reported because "standard immunoassays cannot differentiate acetyl fentanyl from fentanyl."

Other "clandestinely produced fentanyl-like substances, commonly known as designer drugs" have surfaced since the late 1970s and 1980s and been placed on Schedule 1 of the Controlled Substance Act, the Drug Enforcement Administration said.

Due to the "imminent hazard to public safety," today's action by the DEA temporarily places the drug on Schedule 1 under the CSA, and it is effective immediately for up to two years, with a possible extension of one additional year, pending completion of the permanent scheduling process.

The number of Americans dying from heroin overdoses doubled across 28 states in 2012 from 2010, according to the Centers for Disease Control and Prevention, fueled by easy access and rising rates of opioid addiction.

The unusual analysis published today in the CDC’s weekly bulletin stemmed from the agency’s effort to determine if reports from some states about spikes in heroin use and related deaths since 2010 were part of a larger nationwide trend. They found a growing problem with fatal overdoses of heroin.

Health officials have focused in recent years on reducing abuse of prescription opioid painkillers, such as OxyContin. Overdoses of those medicines quadrupled from 1999 through 2010, while heroin, a cheaper and more available alternative, increased by less than 50 percent. The report confirms heroin has made a comeback in 28 states, as noted by Vermont Governor Peter Shumlin who said in January his state was in a “full-blown heroin crisis.”

Deaths from heroin overdoses rose across the board: in both genders, all ages, all racial and ethnic groups and all regions of the country, the CDC report found.

“The findings indicate a need for intensified prevention efforts aimed at reducing overdose deaths from all types of opioids,” the report found. “Efforts to prevent expansion of the number of opioid pain reliever users who might use heroin when it is available should continue.”

Death Toll

There were 3,635 heroin deaths in 2012, an increase from 1,779 two years earlier. While the crackdown on opioid abuse may have led users to heroin, painkillers are still more deadly. Opioid overdoses killed 9,869 Americans in 2012, down 5.4 percent from 2010.

Additional data suggests that prescription painkillers may be a gateway drug to heroin use, the report said. Three-quarters of patients in a rehabilitation program who started using heroin after 2000 said the first opioid they took was a prescription medication. More than 80 percent of people who began using heroin in the 1960s said they started with the drug.

“Reducing inappropriate opioid prescribing remains a crucial public health strategy to address both prescription opioid and heroin overdoses,” said CDC Director Thomas Frieden. “Addressing prescription opioid abuse by changing prescribing is likely to prevent heroin use in the long term.”

An alarming number of drug overdoses has officials in one Bucks County township gearing up for a fight.

In the past month, 63 people have overdosed in Bensalem, Pa. on opioid drugs like heroin and prescription pain killers that include oxycodone and vicodin says township Director of Public Safety Fred Harran.

While heroin is widely known as a dangerous and severely addictive narcotic that’s long been a target of the war on drugs, Harran says it’s the prescription painkillers that are a bigger source of concern.

Between 80 and 90-percent of the crimes committed in the town are tied in one way to drugs, according to Harran. He says the drug seekers are both a mix of local residents and visitors traveling to the town to get high.

Harran and other public safety officials have been meeting to determine an attack plan to cut down on drug use and availability. The director says he’s not ready to release every detail about the plan, but said the department’s actions would be "groundbreaking."

A new report released on Monday from the Trust for America’s Health found Pennsylvania has the 14th highest rate of drug overdose deaths. The report found the Commonwealth had 15.3 overdose deaths per 100,000 residents in 2010. Most of those deaths involved the use of prescription drugs.

In Philadelphia, city officials have seen what they call a startling spike in addiction rates, deaths and confiscations by police of opioids like prescription pills and heroin.

Nationally, drug overdose is the leading cause of injury death in the United States, according to the Centers for Disease Control and Prevention. Drug overdose deaths have jumped 102-percent from 1999 to 2010 and as of the last reporting in 2010, 60-percent of those deaths were related to pharmaceuticals.

The CDC also found that of the 38,329 overdose deaths in 2010 that involved pharmaceuticals, 75-percent involved some form of opioid.

Drug-related fatalities are now at the top of the accidental-death list in a growing number of states, according to a report from the U.S. Centers for Disease Control and Prevention (CDC).

And in the case of one of those drugs, fentanyl, the growth of abuse and increase of deaths from the drug is alarming health officials and families. Fentanyl, an opiate, is much more potent than heroin and results in frequent overdoses that can lead to respiratory depression and death.

CDC has developed an issue brief that summarizes the most recent information about deaths and emergency department visits resulting from drug overdoses. This brief includes information on overdose trends, the most common drugs involved, and the regions and populations most severely affected. Recommendations on how health care providers, private insurance providers, and state and federal agencies can work to prevent unintentional drug overdoses are also included.

During 1999–2006, the number of poisoning deaths in the United States nearly doubled, largely as a result of deaths involving prescription opioid painkillers. CDC researchers found that, in 2006, the rate of poisoning involving opioid painkillers in Washington state was significantly higher than the national rate. Methadone was involved in almost two -thirds of these deaths.

While types of drugs involved in prescription drug overdose deaths can be determined from medical examiner and emergency department data, the patterns of prescription use leading up to these overdoses have not been described. To help in this effort, CDC Injury Center scientists are conducting a study is to compare the prescriptions used among people who died of drug overdoses with the prescription use of a control group of other users of controlled substance prescription drugs (CSPD). This project will link information from the New Mexico prescription drug monitoring program (PDMP) and the New Mexico state medical examiner. Risk factors to be examined will include prescriptions for specific drugs, the number of prescriptions, providers, and pharmacies, and overlapping prescriptions. Study results are expected in 2010.

Millions of Americans with significant or chronic pain associated with their medical problems are being under-treated as physicians increasingly fail to provide comprehensive pain treatment -- either due to inadequate training, personal biases or fear of prescription drug abuse.

A pharmaceutical expert in pain management in the College of Pharmacy at Oregon State University says the issue is reaching crisis proportions, and in two new professional publications argues that health consumers must be aware of the problem and in many cases become more informed, persistent advocates for the care they need and deserve.

Adequate pain treatment has always been a concern, said Kathryn Hahn, a pharmacist, affiliate faculty member at OSU and chair of the Oregon Pain Management Commission, in part because it's not a major part of most physician's medical training. Even though they will often see a stream of patients with pain problems throughout their careers, they may only get a few hours of education on the use of opioids in medical school.

In recent years, the problems have dramatically increased due to concerns about prescription drug abuse, in which drugs such as oxycodone are often stolen from homes or otherwise misused. In a 2006 survey of teenagers, 62 percent said prescription pain relievers were easy to get from their parents' medicine cabinet. One analysis concluded that admissions to federally supported treatment programs for prescription opioid abuse increased 342 percent from 1996 to 2006 -- a comprehensive problem that is also estimated to cost insurance companies tens of billions of dollars a year.

"Surveys show that at least 30 percent of patients with moderate chronic pain and more than 50 percent of those with severe chronic pain fail to achieve adequate pain relief," she wrote in one article. "The economic impact of acute and chronic pain exceeds $100 billion per year in the U.S. alone."

Community pharmacists, she said, are often on the front lines of this issue and constantly see individuals with pain concerns and inadequate pain management by their health care providers. They can often help serve as advocates, improve lines of communication between patients and their doctors, and help patients manage their prescribed drug therapies.

Health insurers also have an important role to play in reducing prescription drug abuse, Hahn said. They can help educate physicians on appropriate use, advocate for universal precautions in use of pain medicines, restrict off-label uses of readily diverted opioids, pay for multidisciplinary pain management programs, and take other steps.

People who develop chronic physical pain often require a combination of the art and science of medicine to reclaim or maintain a normal life. And the clinical laboratory is increasingly weighing in on the scientific side of the pain management equation with testing that can improve the safety and efficacy of opioid and other pain medications.

The lab’s role in pain management includes verifying that patients are taking their prescribed medications as directed and providing therapeutic drug monitoring (drug concentrations) to help determine if the medication is doing what it’s intended to do—“give people relief from pain,” says Paul Jannetto, PhD, assistant professor of pathology and director of clinical chemistry toxicology at the Medical College of Wisconsin in Milwaukee.

The No. 1 reason urine opiate drug screening is done by pain management physicians is to monitor patients for compliance, said Dr. Jannetto in a presentation at the 2008 American Association for Clinical Chemistry meeting. But some clinicians are also using therapeutic drug monitoring and pharmacogenomic testing as part of pain management, especially in difficult cases.

While statistics show that pain testing is underused, says Robert Middleberg, PhD, laboratory director at NMS Laboratories in Willow Grove, Pa., and a consultant to the CAP Toxicology Resource Committee, more and more physicians are interested in it. That’s evident, he adds, by the growing number of pain management labs “sprouting up.” In addition, “insurers are covering the testing at profitable rates for laboratories,” he says, which tells you they see an actuarial benefit to anteing up.

Yet pain management testing is no slam-dunk in terms of always providing easy yes or no answers, even in the realm of urine drug screening, which many physicians require patients who take opioids to undergo continually, Dr. Jannetto said.

On the upside, urine drug screening, which provides a two- to three-day detection window for most opiates, is “fast, automated, inexpensive, and noninvasive” for monitoring patients, he noted. But “screening” is the operative word. The screening tests are typically competitive immunoassays based on competition between drug in the patient’s sample and labeled drug for the antibodies’ binding sites. The antibodies are directed against drug groups or classes—opiates, for example. Thus, they can’t be used to identify or quantitate the concentration of a specific opiate such as morphine, codeine, or heroin. A more specific alternative chemical method (GC/MS) must be used to obtain a confirmed analytical result.

A patient taking prescribed hydrocodone who tests positive on the urine opiate screening assay could have sold that medication and used heroin, morphine, codeine, or even oxycodone, all of which can turn the screening test positive, Dr. Jannetto cautions.

He advises physicians to order confirmatory testing to pinpoint what the patient is really taking in cases, for example, where the person displays erratic behavior in the office or is suspected of diverting the medication.

Confirmatory testing uses mass spectrometry, which, as NMS’ Dr. Middleberg explains, provides “a molecular fingerprint of a compound based on structural characteristics of the substance.” The testing identifies not only the parent drug but also its metabolites, which can be tricky for physicians to interpret without guidance from the laboratory.

Physicians sometimes also receive unexpected negative results from urine drug screens for patients who are supposed to be taking an opioid or other medication. To prevent false-negatives, Dr. Jannetto said, clinicians and labs have to understand what the assays they are using will detect. Interpretation of results must also take into account that urine concentrations can vary extensively with fluid intake and other biological variables. In addition, they should realize that cross-reactivity varies among test manufacturers’ kits.

Oxycodone urine screening assays...cause confusion for the physicians, Dr. Jannetto said, because the lab’s urine opiate screening assay may not cross-react with oxycodone at all or very well. “So doctors will say, ‘My patient is on oxycodone and sometimes tests positive and sometimes not on your assay—what’s going on?’ The answer is that whether the person tests positive may have to do with his or her hydration state and the level of oxyco­done in the urine. The lab actually has a separate oxycodone screen with a lower cutoff that specifically detects oxycodone and its metabolite [oxymorphone],” he said.

Of course, says Gwen McMillin, PhD, the most common reason a drug screen comes back negative is that the patient is not taking the drug or taking it less frequently than prescribed. But “perhaps the patient didn’t realize he had to produce a urine sample until he got to the office, and then drank a lot of fluids to produce the sample,” says Dr. McMillin, assistant professor in the University of Utah Department of Pathology and medical director of toxicology at ARUP Laboratories. “Or the patient could have accelerated metabolism or drug elim­ination, or have an enzyme inducer that’s ramped up his metabolism. In rare cases, a person with Celiac disease or Crohn’s disease might not absorb a medication.”

Some pain patients adulterate their urine samples so they’ll test negative for illicit drugs. Dr. Jannetto sees such samples about five percent of the time in his laboratory. The patient can drink a lot of water to dilute the urine, which drops the drug below the cutoff on a screening assay. The alternative is to add products to the urine that contain acid, nitrites, and various other compounds that interfere with the immunoassays, he said. Third, patients can buy drug-free urine on the Internet.

Pain management physicians typically do not do witnessed urine collections, Dr. Jannetto noted. But simple countermeasures can help flag potentially adulterated samples. You can test the urine-specific gravity to identify very dilute urine, and look at the pH to make sure the patient hasn’t added acid to the sample. “If the pH is less than 3, that’s suspicious.”

Dr. Jannetto routinely advises physicians doing pain management testing to run creatinine on urine samples, which is very cost-effective.

“If the creatinine is less than 20 mg/dL, that person is well hydrated,” which the physician might consider when interpreting negative results, he advised. Some samples his labor­atory receives “have no creatinine [<5 mg/dL], urea, no nothing ...” And that, of course, isn’t human urine.

Urine screening is most vulnerable to sample tampering that affects results. But some forms of adulteration, Dr. Middleberg says, can also affect mass spectrometry results, even when the lab is using state-of-the-art technology. That’s one reason labs do adulteration testing in the form of pH, nitrites, oxidants, and creatinine, he says. Nitrites, which are in products used to adulterate urine testing, “tend to have a particular effect on the ability to measure can­nabinoids in urine by mass spectrometry,” he says, “especially depending on the pH of the urine.”

Urine drug monitoring using mass spectrometry won’t detect patients taking a higher dose of a drug than prescribed, Dr. Middleberg says. The clinician could “attempt to get at that with blood or serum testing, but even there you have to consider [pharmacogenomics] and other pharmacokinetic differences, so it’s never easy.”

While not widely used, therapeutic drug monitoring on blood samples can help physicians manage more complex cases. “Great candidates” for TDM, says Loralie Langman, PhD, associate professor at Mayo College of Medicine and director of the toxicology and drug monitoring laboratory at Mayo Clinic in Rochester, Minn., are patients who are “atypical”—that is, requiring higher or lower doses of a drug or experiencing significant adverse drug reactions.

Physicians who use TDM to troubleshoot, however, will be somewhat in the dark without the patient’s baseline because “what’s toxic in one person may be therapeutic in another,” she notes. Yet that can change for an individual patient as the person develops tolerance to the opioid. “Performing TDM is not a bad idea” when dealing with a drug that doesn’t have a well-established therapeutic range or is known to have a large interpatient variability, especially when compliance is an issue, Dr. Langman says.

As for pharmacogenomic testing, Dr. Jannetto says physicians rarely test for CYP2D6, an enzyme responsible for metabolizing 20 to 25 percent of prescription medication and over-the-counter products. “And in the case of opioids/opiates—oxycodone, hydrocodone, and codeine —it’s an important player.”

A poor metabolizer of CYP2D6, which two to 10 percent of most ethnic groups are, says Dr. Jannetto, will build up higher concentrations of the parent drugs oxycodone or hydro­codone, and may end up with more side effects. “In the case of co­deine, poor metabolizers of CYP2D6 won’t get any pain relief because the analgesic properties of codeine come from its CYP2D6 metabolite morphine.”

As an alternative to doing CYP2D6 genotype testing, the clinician can also identify poor metabolizers by doing TDM. But even if clinicians identify a poor metabolizer, says Dr. Jannetto, there are no formal guidelines for how to adjust the person’s pain medication dosages. Thus, “option B,” he adds, may be to start the person on a low dose of an opioid and titrate it up until the person gets pain relief. Or the clinician could put the person on a medication metabolized by a different enzyme. “Fentanyl is one option, as it’s metabolized by 3A4 and 3A5. Methadone is metabolized by multiple pathways, so that’s another option.”

Other medications a patient is taking can also inhibit CYP2D6, causing the patient to function as a poor metabolizer. For that and other reasons, pain management physicians or those prescribing pain medications should always ask the patient for a complete list of the medications he or she is taking, including over-the-counter medications and herbals, Dr. Jannetto says.

TDM and PGx testing combined not only optimize pain management in some cases but also increase safety for patients and for clinicians medico­legally when prescribing opioids.

The bottom line in pain management, she says, is to treat pain safely and adequately so patients no longer have to do what some in her care have described: “expend a huge amount of energy trying to isolate the pain into a corner of their day or life ... like a lion-tamer having to keep the lion at a distance.”